title: New molecular targets beyond KIT and PDGFRA in gastrointestinal stromal tumors: present and future.
abstract: BACKGROUND
  The biological complexity of gastrointestinal stromal tumors (GISTs) and the concomitant increase in patients' life expectancy have enhanced the need for new therapeutic options to overcome the development of primary and secondary resistance to tyrosine kinase inhibitors. Aided by more sophisticated molecular biology techniques, researchers have recently sought to identify new therapeutic targets with a defined role in GISTs pathogenesis and a potential application in clinical practice.
  
  
  METHODS
  The first aim of this review is to describe new targets and drugs in GISTs, alone or in combination, both in pre-clinical and clinical settings. The second aim is to discuss the criticism in this field, the role of molecular biology, and future perspectives in light of the recent development of more sophisticated whole-genomic technologies.
  
  
  CONCLUSIONS
  Several targets involved in GIST pathogenesis have been identified and novel biological drugs have recently been developed, offering new treatment options in the scenario of GIST therapy. However, the identification of new therapeutic targets represents a long process and requires a global overview of the problem and a multi-step approach to convert an initial intuition or casual finding into a systematic analytical process.
authors.affiliation: University of Bologna, S.Orsola-Malpighi Hospital, Department of Hematology and Oncological Sciences, Bologna, Italy. maggie.nannini@gmail.com
authors.forename: Margherita
authors.initials: M
authors.lastname: Nannini
authors.forename: Guido
authors.initials: G
authors.lastname: Biasco
authors.forename: Alessandra
authors.initials: A
authors.lastname: Maleddu
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pantaleo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D006801:Humans; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha